Effects of Progesterone on IV Nicotine-Induced Changes in Hormones and Subjective Ratings of Stimulant Drug Effect

This study has suspended participant recruitment.
(Clinical studies are stopped, pending funding.)
Sponsor:
Information provided by (Responsible Party):
Nancy Kishlar Mello, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01589081
First received: April 27, 2012
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

The proposed clinical studies will analyze the interactions between progesterone, nicotine, alterations in endocrine hormones, mood and cardiovascular measures. It is hypothesized that the administration of progesterone at a dose that mimics luteal phase levels in normal cycling women will diminish the positive subjective effects of nicotine, as has been consistently observed for cocaine. This novel approach could have direct implications for facilitating smoking cessation treatment in women of reproductive age


Condition Intervention
Nicotine Dependence
Drug: Intravenous Nicotine
Drug: Progesterone

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Effects of Progesterone on IV Nicotine-Induced Changes in Hormones and Subjective Ratings of Stimulant Drug Effect

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Effects of Progesterone on IV nicotine hormones and mood [ Time Frame: From baseline to study completion (approximately 1 year) ] [ Designated as safety issue: No ]
    We are examining the effects of progesterone on IV nicotine induced changes in serum/plasma hormone levels and subjective states, as measured by a visual analog scale.


Estimated Enrollment: 45
Study Start Date: September 2008
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Female Smokers (Luteal Phase) Drug: Intravenous Nicotine
Subjects will be given an IV challenge dose of nicotine or placebo in a constant volume of 2 mL on any study session day. The nicotine solutions (1.0 mg/70kg or 1.5 mg/70kg or 2.0 mg/70kg) will be administered over 1 min. This rate of drug delivery (2 mL over one minute) has been safe in our IRB-approved studies of nicotine. Most investigators have administered nicotine over 10 seconds without any adverse reactions. We concur with the IRB recommendation that the lower doses (1.0 mg/70kg; and 1.5 mg/70kg) will be administered first and the higher dose (2.0 mg/70kg) will be administered last.
Other Name: IV Nicotine
Drug: Progesterone
To stimulate the luteal phase of the menstrual cycle, Prometrium capsules containing 200 mg of micronized progesterone or placebo (lactose containing) capsules will be administered orally at 120 minutes before the injection of IV nicotine.
Active Comparator: Female Smokers (Follicular Phase) Drug: Intravenous Nicotine
Subjects will be given an IV challenge dose of nicotine or placebo in a constant volume of 2 mL on any study session day. The nicotine solutions (1.0 mg/70kg or 1.5 mg/70kg or 2.0 mg/70kg) will be administered over 1 min. This rate of drug delivery (2 mL over one minute) has been safe in our IRB-approved studies of nicotine. Most investigators have administered nicotine over 10 seconds without any adverse reactions. We concur with the IRB recommendation that the lower doses (1.0 mg/70kg; and 1.5 mg/70kg) will be administered first and the higher dose (2.0 mg/70kg) will be administered last.
Other Name: IV Nicotine
Drug: Progesterone
To stimulate the luteal phase of the menstrual cycle, Prometrium capsules containing 200 mg of micronized progesterone or placebo (lactose containing) capsules will be administered orally at 120 minutes before the injection of IV nicotine.

Detailed Description:

These clinical studies are designed to examine the effects of progesterone on IV nicotine induced changes on anterior pituitary (ACTH, LH, and Prolactin) and adrenal hormones (DHEA and cortisol). We also plan to study norepinephrine (NE) and epinephrine (E), because nicotine stimulates rapid release of NE and E in preclinical and clinical studies. The study will examine the acute effects of progesterone on the effects of IV nicotine on the HPG axis. Progesterone's influence on the acute effects of nicotine on the gonadal steroid hormones (estradiol, testosterone, progesterone) are unknown. The effects of progesterone on nicotine induced changes on gonadal steroid hormones and the reciprocal feedback regulation by LH will also be examined. The temporal covariance of progesterone influenced hormonal changes with serum nicotine levels and nicotine-induced changes in subjective states and cardiovascular measures will be analyzed. Finally, the covariance between the effects of progesterone on nicotine-induced changes in endocrine, subjective and cardiovascular effects and the temporal concordance with increases in serum nicotine and cotinine levels will be determined.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Women between the ages of 18 and 40 who currently smoke at least 15 cigarettes every day, and who fulfill DSM-IV diagnostic criteria for nicotine dependence will be eligible for participation.
  • No evidence of clinically significant disease based upon complete medical history and physical examination supervised by Dr. Arthur Siegel (Chief of Internal Medicine).
  • Absence of DSM-IV Axis I Disorders other than nicotine dependence (305.10) as measured by the Structured Clinical Interview (SCID).
  • Routine laboratory blood tests including complete blood count, electrolytes, BUN and creatinine, liver function tests, hepatitis panel and urinalysis will be performed. Laboratory parameters must be within the normal range. HBsAg must be negative but subjects who have hepatitis serology consistent with previous exposure to Hepatitis A, Hepatitis B, or Hepatitis C, but who do not have clinical and biochemical evidence of acute infection, will be acceptable.
  • Hematocrit levels ≥ 35% for females.
  • Serum pregnancy test (hCG beta subunit) results must be negative within 24 hrs of the study session day.
  • Normal EKG.
  • A Body Mass Index (BMI—ratio of weight (W) to height (H) squared; W/H2=kg/m2) of between 18.0 and 27.0 for women.
  • Subjects must be able to read and understand instructions, as well as provide a valid informed consent.

Exclusion Criteria:

  • Participants with any lifetime DSM-IV Axis I disorder other than nicotine dependence.
  • Participants with clinically significant medical disorders.
  • Women who are pregnant as determined by laboratory testing for serum beta hCG.
  • Women who use hormonal contraceptive medications will not be accepted, because this would confound the hormonal measures.
  • Women with a mean BMI of outside the range 18.0-27.0.
  • Subjects with peanut/peanut oil allergies will be excluded.
  • Participants diagnosed with lactose intolerance will be excluded.
  • Participants who describe themselves as seeking treatment will not be selected but will be referred to local smoking cessation programs.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01589081

Locations
United States, Massachusetts
Alcohol and Drug Abuse Research Center at McLean Hospital
Belmont, Massachusetts, United States, 02478
Sponsors and Collaborators
Mclean Hospital
Investigators
Principal Investigator: Nancy K Mello, PhD Mclean Hospital
  More Information

No publications provided

Responsible Party: Nancy Kishlar Mello, Director, Alcohol and Drug Abuse Research Center & Professor of Psychology (Neuroscience), Harvard Medical School, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01589081     History of Changes
Other Study ID Numbers: 2008-p-000454
Study First Received: April 27, 2012
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Mental Disorders
Central Nervous System Stimulants
Nicotine polacrilex
Nicotine
Progesterone
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 28, 2014